Age-determined severity of anti-myeloperoxidase autoantibody-mediated glomerulonephritis in mice
| Autor: | Elisabeth Brouwer, Arjen H. Petersen, Peter Heeringa, Qi Wang, Jill Moser, Annemieke M. H. Boots, Jun Yuan, Mirjan M. van Timmeren, Johanna Westra |
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| Přispěvatelé: | Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Translational Immunology Groningen (TRIGR), Microbes in Health and Disease (MHD), Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT), Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aging ANCA-ASSOCIATED VASCULITIS mouse model Inflammation inflamm-ageing SYSTEMIC VASCULITIS LIPOPOLYSACCHARIDE Severity of Illness Index Immunoglobulin G Mice 03 medical and health sciences Immune system WEGENERS-GRANULOMATOSIS KIDNEY INFLAMMATION medicine Animals IN-VIVO Autoantibodies Peroxidase Transplantation Kidney biology business.industry Autoantibody Glomerulonephritis medicine.disease Mice Inbred C57BL KLOTHO Disease Models Animal 030104 developmental biology medicine.anatomical_structure Nephrology ageing ENDOTHELIUM Myeloperoxidase Immunology Albuminuria biology.protein Female medicine.symptom business glomerulonephritis NEUTROPHIL |
| Zdroj: | Nephrology, Dialysis, Transplantation, 32(2), 254-264. Oxford University Press |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfw202 |
| Popis: | BACKGROUND: Anti-neutrophil cytoplasmic antibody associated vasculitis (AAV) is a typical disease of the elderly. In AAV, there is an age-specific increase in disease incidence with age being a predictor of disease outcome. In this study, we aimed to determine the contribution of age to the development of AAV employing a mouse model of anti-myeloperoxidase (MPO) antibody-mediated glomerulonephritis.METHODS: Anti-MPO IgG and lipopolysaccharide (LPS)-mediated glomerulonephritis was induced in 3- and 18-month-old C57Bl6 mice. Clinical and pathological parameters of disease severity, alterations in the immune system and kidney specific changes in these mice were evaluated.RESULTS: Eighteen-month-old mice developed increased disease severity upon injection of anti-MPO IgG/LPS compared with 3-month-old mice. This was evidenced by increased albuminuria, more extensive glomerular capillary necrosis and increased glomerular neutrophil accumulation. Glomerular crescent formation was mild in both young and old mice. Old mice displayed higher plasma interleukin-6 levels as well as higher proportions of circulating neutrophils and activated monocytes compared with young mice. In addition, renal mRNA levels of inflammatory genes and endothelial adhesion molecules were higher in 18-month-old mice compared with 3-month-old mice.CONCLUSION: In conclusion, our results indicate that aged mice develop more severe clinical and pathological disease upon induction of anti-MPO IgG/LPS-mediated glomerulonephritis. These findings may be attributed to age-related changes in the immune system as well as in the kidney itself. |
| Databáze: | OpenAIRE |
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